Community indicators for mental health in Europe: a scoping review.

Background: Community indicators may predict and influence individuals` mental health, and support or impede mental health management. However, there is no consensus on which indicators should be included in predictions, prognostic algorithms, or management strategies for community-based mental health promotion and prevention approaches. Therefore, this scoping review provides an overview of relevant community-level indicators for mental health in the general as well as risk populations in a European context. Methods: We conducted a scoping review in the following electronic databases: PubMed, Embase, and PsycInfo. Eligible studies focused on context factors such as either the physical or social environment, reporting at least one mental health outcome and referring to a European population. Publications between 2012 and March 8, 2022 are considered. Results: In total, the search yielded 12,200 identified records. After the removal of duplicates, 10,059 records were screened against the eligibility criteria. In total, 169 studies were included in the final analysis. Out of these included studies, 6% focused on pan-European datasets and 94% on a specific European country. Populations were either general or high-risk populations (56 vs. 44%, respectively) with depressive disorder as the main reported outcome (49%), followed by general mental health (33%) and anxiety (23%). Study designs were cross-sectional studies (59%), longitudinal (27%), and others (14%). The final set of indicators consisted of 53 indicators, which were grouped conceptually into 13 superordinate categories of community indicators. These were divided into the domains of the physical and social environment. The most commonly measured and reported categories of community indicators associated with mental health outcomes were social networks (n = 87), attitudinal factors toward vulnerable groups (n = 76), and the characteristics of the built environment (n = 56). Conclusion: This review provides an evidence base of existing and novel community-level indicators that are associated with mental health. Community factors related to the physical and social environment should be routinely recorded and considered as influencing factors or potentially underestimated confounders. The relevance should be analyzed and included in clinical outcomes, data, monitoring and surveillance as they may reveal new trends and targets for public mental health interventions.

Speech Rhythm Variation in Early-Stage Parkinson's Disease: A Study on Different Speaking Tasks.

Patients with Parkinson's disease (PD) usually reveal speech disorders and, among other symptoms, the alteration of speech rhythm. The purpose of this study is twofold: (1) to test the validity of two acoustic parameters-%V, vowel percentage and VtoV, the mean interval between two consecutive vowel onset points-for the identification of rhythm variation in early-stage PD speech and (2) to analyze the effect of PD on speech rhythm in two different speaking tasks: reading passage and monolog. A group of 20 patients with early-stage PD was involved in this study and compared with 20 age- and sex-matched healthy controls (HCs). The results of the acoustic analysis confirmed that %V is a useful cue for early-stage PD speech characterization, having significantly higher values in the production of patients with PD than the values in HC speech. A simple speaking task, such as the reading task, was found to be more effective than spontaneous speech in the detection of rhythmic variations.

Improving survival with deferiprone treatment in patients with thalassemia major: a prospective multicenter randomised clinical trial under the auspices of the Italian Society for Thalassemia and Hemoglobinopathies.

The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone-deferoxamine (DFP-DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared deferoxamine (DFO) versus DFP alone, sequential DFP-DFO, or combined DFP-DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP-DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP-DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant (p-value<0.013). For each increasing year of age, the hazard ratio for males was 1.03 higher than that for females (p-value<0.013). In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are deferoxamine-treatment, complications, and the interaction effect of sex and age.

The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis.

Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM-patients, suggesting their involvement in the pathogenesis of beta TM-osteoporosis.

Risk factors for death in patients with beta-thalassemia major: results of a case-control study.

This retrospective one to one matched case-control study was aimed at evaluating risk factors for death in beta-thalassemic patients followed in Italian centers between 1997 and 2001. The mortality risk was lower in patients with good compliance to iron chelation therapy and in those treated with deferiprone.

Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: new pieces of the puzzle.

UNLABELLED: Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis. INTRODUCTION: Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss. MATERIALS AND METHODS: We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin. RESULTS: Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio. CONCLUSIONS: Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients.

Clinical and histological characterization of liver disease in patients with transfusion-dependent beta-thalassemia. A multicenter study of 117 cases.

BACKGROUND AND OBJECTIVES: Updated information on liver disease in transfusion-dependent beta-thalassemia is lacking. We conducted a multicenter study within the Cooleycare Group to describe the clinical and histopathological features of liver disease in currently treated thalassemics. DESIGN AND METHODS: Two-hundred and three thalassemics with laboratory signs of liver disease were eligible. Liver biopsy was performed in the 129 (63.5%) who consented (age 26+/-7 years). Biological samples were sent to the central laboratory. RESULTS: Anti-hepatitis C virus (HCV) antibodies were found in 118 patients (91%), 85 (72%) of whom were viremic. Ninety-one patients (70%) had abnormal aminotransferase concentrations. In the 117 liver biopsies that met the criteria for evaluation (88%), the median Ishak's necroinflammatory and fibrosis scores were 4 (range, 0-9) and 2 (range, 0-6), respectively. Significant fibrosis (score >or=3) was found in 53 (45%); 9 (8%) had cirrhosis. At multivariate analysis, necroinflammation was related to HCV viremia, and fibrosis to increased serum aminotransferases, higher iron stores (including serum ferritin, Deugnier's total iron score, and liver iron content) and male gender (p<0.05). In HCV-RNA negative subjects, the median total iron score was 27 (range, 0-52). Iron accumulated in both mesenchymal cells and hepatocytes, and the presence of a lobular gradient was interpreted to indicate intestinal hyperabsorption. INTERPRETATION AND CONCLUSIONS: Transfusion-dependent thalassemics have mild liver necroinflammation, mainly attributable to HCV infection. Significant fibrosis is frequent, and its progression is mostly influenced by iron overload which, with current therapy regimens, may be attributable to both erythrocyte catabolism and iron hyperabsorption.

Validation of dHPLC for molecular diagnosis of beta-thalassemia in Southern Italy.

Beta-thalassemia, the most common hereditary anemia in the Mediterranean area, results from over 200 causative mutations in the beta-globin locus. The aim of this study was to validate a denaturing high-performance liquid chromatography (dHPLC)-based assay for postnatal and prenatal molecular diagnosis of beta-thalassemia in Southern Italy. Sixty beta-thalassemic patients, affected either by thalassemia intermedia or thalassemia major, were analyzed in a blind study. We also carried out prenatal molecular diagnosis in 12 couples at-risk for having affected offspring. Chorionic villi samples were subjected to dHPLC analysis upon molecular characterization of the parental beta-globin alleles. Direct sequence analysis was used to validate each result, showing an accuracy rate of 100% for dHPLC. Overall, our protocol was able to identify the responsible mutations in all 96 analyzed subjects (including 12 prenatals in at-risk pregnancies), detecting the eight most common mutations in Southern Italy. Three rare mutations (one of which, reported here for the first time) that standard mutation detection methods failed to reveal, were also identified. dHPLC assay proved to be a reliable, rapid, and sensitive method for detecting both common and rare mutations within the beta-globin gene. Because of this property our protocol has the potential to be implemented for mutational screening in different areas of high prevalence for beta-thalassemia.

Role of genetic pattern on bone mineral density in thalassemic patients.

OBJECTIVES: To evaluate the role of genetic background in osteoporosis/osteopenia development in beta-Thalassemia Major patients. DESIGN AND METHODS: The influence of VDR (FokI, BsmI) as well as COLIA1 (Sp1) gene polymorphisms on BMD was investigated in 40 patients. RESULTS: Although the examined gene polymorphisms did not significantly affect BMD variations in our population, BsmI was found to display beneficial effects on patient response to alendronate therapy. CONCLUSION: Genetic factors retain a potential role for improvement of osteoporosis management in thalassemic patients.

Asymptomatic cholelithiasis in children with sickle cell disease: early or delayed cholecystectomy?

SUMMARY BACKGROUND DATA: Our study aimed to evaluate the role of elective laparoscopic cholecystectomy (LC) in children with sickle cell disease (SCD) and asymptomatic cholelithiasis and, furthermore, to determine whether the outcome is related to the operation timing. METHODS: The records of 30 children with SCD diagnosed with cholelithiasis from June 1995 to September 2005 were retraspectively reviewed. All 30 children were asymptomatic at the time of the first visit, and an elective LC was proposed to all of them. The operation was accepted in the period of study by 16 children and refused by 14. During medical observation, 10 of the 14 children who refused surgery were admitted for severe biliary colics. Acute cholecystitis was diagnosed by abdominal ultrasound in 3 cases and in 1 case choledocholithiasis, ultrasonographically suspected, was confirmed by magnetic resonance cholangiopancreatography (MRCP) and treated during endoscopic retrograde cholangiopancreatography (ERCP). All children, emergency admitted, underwent LC after the onset of symptoms. The patients were divided up into 2 groups (A: asymptomatic; B: symptomatic) depending on clinical presentation and operation timing and the respective outcomes were compared. RESULTS: Elective LC in asymptomatic children (group A) is safe with no major complications reported. During medical observation in children who refused elective surgery (group B), 6 biliary colics, 3 acute cholecystitis, and 1 choledocholithiasis were observed. Three sickle cell crises occurred in symptomatic children during biliary colics. The correlation between cholecystectomy performed in asymptomatic children (group A) and cholecystectomy performed in symptomatic children (group B) showed significant differences in the outcome. Morbidity rate and postoperative stay increased when children with SCD underwent emergency LC. CONCLUSIONS: Elective LC should be the gold standard in children with SCD and asymptomatic cholelithiasis to prevent the potential complications of biliary colics, acute cholecystitis, and choledocholithiasis, which lead to major risks, discomfort, and longer hospital stay.

Iron burden and liver fibrosis decrease during a long-term phlebotomy program and iron chelating treatment after bone marrow transplantation.

In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life.

Long-term treatment with deferiprone in a L1 veteran.

We studied a patient with mild beta-thalassaemia major under treatment with the oral chelator deferiprone (DFP or L1) for about 10 yr (L1 veteran). Due to poor compliance with desferrioxamine, the patient started compassionate use of DFP at an age of 23 yr with a serum ferritin of 5200 microg/L. Monitoring iron overload by SQUID biosusceptometry revealed a dramatic decrease of liver iron concentrations from 4500 to 950 microg/g(liver) within 9.5 yr. A good clinical response to chelation treatment with DFP was observed together with an improvement of liver and cardiac function and a reduction in the hepatitis virus load.

Role of polymorphic sequences 5' to the G(gamma) gene and 5' to the beta gene on the homozygous beta thalassemic phenotype.

Sixty-seven homozygous male and female thalassemic patients with different phenotypes, aged between 8 and 33 years, were divided into three groups, according to the severity of their beta-thalassemia (thal) mutations. We investigated whether some co-inherited genetic factors could influence the phenotype. Patients with milder beta-thal defects, homozygotes or compound heterozygotes for the IVS-I-6 (T-->C) or -87 (C-->G) mutations had a milder disease. In addition, determination of the co-inheritance of the -158 (C-->T) G(gamma) polymorphism and the (AT)9T5 repeat motif in the region -540 to -525, 5' to the beta-globin gene, showed that in some patients with severe or mild/severe beta-thal mutations, linked to haplotype III, there was higher Hb F expression. We conclude that in homozygous beta-thal patients, the severity of the mutations is the most important factor influencing the phenotype, but some polymorphisms such as the -158 (C-->T) G(gamma) and (AT)9T5 repeat motif, increasing the Hb F expression and ameliorate the clinical course of the disease.